反应详情

To a mixture of dimethyl-[1-(4-morpholin-4-yl-2-tributylstannanyl-thieno[3,2-d]pyrimidin-6-ylmethyl)-piperidin-4-yl]-amine (250 mg, 0.396 mmol), 1-benzenesulfonyl-3-bromo-7-fluoro-1H-indole (163 mg, 0.460 mmol), copper(I) thiophene-2-carboxylate (37 mg, 0.19 mmol), and Pd(PPh3)4 (44 mg, 0.038 mmol) was added THF (2 mL). The reaction vessel was evacuated and back filled with argon. The reaction mixture was diluted with hexane, filtered through a plug of solka floc, and the filtrate was concentrated. The residue was triturated with hexane and then purified by flash chromatography (silica, 0-10% MeOH/NH4OH (9:1) in DCM). The elutant was then concentrated to give an off-white solid which was taken up in ethanol (2 mL). A 1 M aqueous NaOH solution (0.25 mL) was then added and the resulting mixture was stirred at reflux for 2 hours. The reaction mixture was concentrated and triturated with water. The crude product was purified by flash chromatography (silica, 0-10% MeOH/NH4OH (9:1) in DCM) to give 118 as an off white solid (41.5 mg, 30%). LCMS: M+H+=495. 1H-NMR (300 MHz, DMSO-d6): δ 12.1 (s, 1H), 8.38 (d, 1H), 8.19 (d, 1H), 7.32 (s, 1H), 7.08 (m, 1H), 6.98 (m, 1H), 3.96 (m, 4H), 3.81 (m, 6H), 2.93 (d, 2H), 2.16 (s, 6H), 2.05 (t, 3H), 1.72 (d, 2H), 1.40 (m, 2H)

1. customThe reaction vessel was evacuated
2. additionback filled with argon
3. additionThe reaction mixture was diluted with hexane
4. filtrationfiltered through a plug of solka floc
5. concentrationthe filtrate was concentrated
6. customThe residue was triturated with hexane
7. custompurified by flash chromatography (silica, 0-10% MeOH/NH4OH (9:1) in DCM)
8. concentrationThe elutant was then concentrated
9. customto give an off-white solid which
10. temperatureat reflux for 2 hours
11. concentrationThe reaction mixture was concentrated
12. customtriturated with water
13. customThe crude product was purified by flash chromatography (silica, 0-10% MeOH/NH4OH (9:1) in DCM)